PB1934: REAL-WORLD OUTCOMES OF ECULIZUMAB TREATMENT IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINUREA: A SYSTEMATIC LITERATURE REVIEW AND EVIDENCE SYNTHESIS
Authors: J.-I. Nishimura, E. Popoff, A. Cheung, A. Wang, I. Tomazos, J. Szer
Journal: HemaSphere (2022)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, hematologic disorder characterized by uncontrolled terminal complement activation, thrombotic events (TEs) and increased morbidity and mortality. The complement component 5 (C5) inhibitor eculizumab has been the standard of care for treating patients with PNH since approval by the US Food and Drug Administration and European Medicines Agency in 2007. Although randomized controlled trials have demonstrated the clinical efficacy and safety of eculizumab, there is a paucity of real-world effectiveness data. Aims: To describe the real-world effectiveness of eculizumab treatment in patients with PNH. Methods: A systematic literature review (SLR) and grey literature search was conducted to identify published observational studies that reported outcomes of eculizumab treatment in patients (aged ≥18 years) with PNH. The search was performed using MEDLINE, Embase and the Cochrane Library from database inception to July 2021. Outcomes of interest included lactate dehydrogenase (LDH) levels, transfusion requirement, units of red blood cells (RBCs) transfused, TEs and mortality. A feasibility assessment for meta-analyses was also performed. Results: The search identified 2,622 unique records, of which 28 were eligible for inclusion (patient sample range: 6–1,807). Of the included studies, 15 (53.6%) utilized a prospective, observational study design and, aside from seven multinational studies, data from 11 unique countries were reported. Meta-analyses were not feasible owing to the considerable heterogeneity in study populations, assessment time points, outcome reporting and definitions. The median age of patients at assessment ranged from 23–56 years and the proportion of male patients was 32–83%. Median PNH disease duration ranged from 2.1–11.0 years (5 studies). Duration of follow-up varied from 11 weeks to 10 years (12 studies). LDH levels following eculizumab treatment were reported in 10 studies and all demonstrated a reduction from baseline levels. The mean (standard error; SE) change in LDH ranged from –338.0 (87.3; mean [SE] baseline LDH = 581.0 [94.9] U/L; n = 11) to –3,101.0 (569.9; mean [SE] baseline LDH = 3,552.0 [584.6] U/L; n = 12) U/L. Amongst studies that had non-zero baseline values, the reduction in transfusion dependence following eculizumab treatment ranged from 15.0% (baseline proportion, 23.0%; n = 231) to 80.0% (baseline proportion, 100.0%; n = 5). The mean (SE) reduction in units of RBCs transfused following eculizumab treatment was reported in six studies and ranged from 1.5 (1.1; n = 6) to 14.3 (1.4; n = 75). TEs following eculizumab treatment were described in 11 studies and ranged from 0.0% (baseline TEs, 0.0–33.3%; n = 5–105) to 9.0% (baseline TEs, 40.9%; n = 22). All-cause mortality among eculizumab-treated patients was reported in six studies and ranged from 0.0% (n = 17–105) to 7.3% (n = 123). These deaths were not related to eculizumab. Summary/Conclusion: This SLR synthesized real-world outcomes associated with complement C5 inhibition in patients with PNH and demonstrated consistent effectiveness of eculizumab beyond the clinical trial setting. Although the heterogeneity of study populations precluded meta-analyses of outcomes data, consistent improvements in key clinical parameters were widely reported, including reductions in LDH levels, TEs, transfusion dependence and mortality outcomes. This analysis further reinforces the benefits of complement C5 inhibition in patients with PNH.